Alcohol metabolism, alcoholic liver disease and alcoholism

Question 1

How much alcohol should we consume maximum?

Answer 1

14 Units

Question 2

What is the equivalent of 1 unit of alcohol?

Answer 2

< 100mls glass of wine

Question 3

How is alcohol metabolized by the liver?

Answer 3

Alcohol is metabolized by the liver through various enzymatic reactions.

Question 4

What are the consequences of alcohol metabolism?

Answer 4

Alcohol metabolism can have various effects on key liver metabolic pathways.

Question 5

What are some key enzymes, metabolites, and cofactors involved in alcohol metabolism?

Answer 5

Various enzymes, metabolites, and cofactors play a role in alcohol metabolism.

Question 6

Can alcohol be stored in the body?

Answer 6

no

Question 7

Where does alcohol metabolism mainly occur?

Answer 7

Alcohol metabolism mainly occurs in the liver.

Question 8

What are the products of alcohol metabolism?

Answer 8

The products of alcohol metabolism are acetaldehyde and acetate.

Question 9

What are the key enzymes involved in alcohol metabolism?

Answer 9

Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are the key enzymes involved in alcohol metabolism.

Question 10

Where is alcohol dehydrogenase located?

Answer 10

Alcohol dehydrogenase is located in the cytosol of the cell.

Question 11

Which tissues have the highest amount of alcohol dehydrogenase?

Answer 11

The liver has the highest amount of alcohol dehydrogenase, followed by the gastrointestinal (GI) tract, kidneys, nasal mucosa, testes, and uterus.

Question 12

What factors can influence the affinity of alcohol dehydrogenase for alcohol?

Answer 12

Factors such as genetic makeup, gender, and other factors can influence the affinity of alcohol dehydrogenase for alcohol.

Question 13

How do individuals of Asian descent and northern Europeans differ in alcohol metabolism?

Answer 13

Individuals of Asian descent who have the B2 ADH isoform metabolize ethanol 20% faster than northern Europeans who possess the B1 ADH.

Question 14

What is the consequence of methanol metabolism?

Answer 14

Methanol metabolism can lead to the production of formaldehyde and formic acid, which are toxic to cells.

Question 15

How does formic acid affect the body?

Answer 15

Formic acid inhibits complex IV of the electron transport chain, leading to the inhibition of ATP production.

Question 16

Which cells are particularly sensitive to formic acid toxicity?

Answer 16

Optic nerve cells are particularly sensitive to formic acid toxicity, which can result in their destruction and blindness.

Question 17

How is ethylene glycol metabolized?

Answer 17

Ethylene glycol is metabolized by alcohol dehydrogenase, producing glycoaldehyde, which is further oxidized to glycolic acid by aldehyde dehydrogenase.

Question 18

What enzyme oxidizes glycolic acid to glyoxylic acid?

Answer 18

Lactate dehydrogenase oxidizes glycolic acid to glyoxylic acid.

Question 19

What is the primary cause of metabolic acidosis in ethylene glycol poisoning?

Answer 19

The accumulation of glycolic acid is primarily responsible for metabolic acidosis.

Question 20

What can glyoxylic acid be further metabolized into?

Answer 20

Glyoxylic acid can be further metabolized into non-toxic glycine, α-hydroxy β-adipic acid, or oxalic acid, which can deposit as crystals in the kidney.

Question 21

What is the effect of alcohol oxidation on the NAD+/NADH ratio?

Answer 21

Alcohol oxidation generates NADH, disturbing the usual cellular NAD+/NADH ratio.

Question 22

How does the decreased NAD+/NADH ratio affect liver metabolic pathways?

Answer 22

The decreased NAD+/NADH ratio profoundly affects liver metabolic pathways, shifting from oxidative, catabolic processes to reductive synthetic processes.

Question 23

What are some liver metabolic pathways affected by the decreased NAD+/NADH ratio?

Answer 23

The affected liver metabolic pathways include glycolysis, citric acid cycle, pyruvate dehydrogenase, fatty acid oxidation, and gluconeogenesis.

Question 24

How does excess NADH caused by alcohol oxidation affect the TCA cycle?

Answer 24

Excess NADH inhibits citrate synthase, slowing down the TCA cycle.

Question 25

What is the consequence of the slowed TCA cycle?

Answer 25

The slowed TCA cycle results in an increase in the key intermediate Acetyl CoA.

Question 26

What happens to NADH produced during ethanol oxidation?

Answer 26

The NADH produced can be recycled back to NAD+ by the electron transport chain.

Question 27

What is the result of excess NADH caused by alcohol oxidation in terms of ketone body production?

Answer 27

Excess NADH leads to the accumulation of Acetyl CoA, which produces ketone bodies through ketogenesis (acetoacetate, β-hydroxybutyrate, and acetone).

Question 28

What is the consequence of higher levels of ketone bodies in the blood?

Answer 28

Higher levels of ketone bodies in the blood result in a state called ketosis.

Question 29

How does excess NADH caused by alcohol oxidation affect fatty acid metabolism?

Answer 29

Excess Acetyl CoA and NADH stimulate fatty acid synthesis over β-oxidation.

Question 30

What happens to the fatty acids synthesized in excess due to alcohol oxidation?

Answer 30

The excess fatty acids are used to synthesize triglycerides, which are then deposited in hepatocytes as lipid droplets, leading to conditions like fatty liver and hyperlipidemia.

Question 31

What is the consequence of the slowed TCA cycle caused by excess NADH?

Answer 31

The slowed TCA cycle contributes to the accumulation of Acetyl CoA, which further affects fatty acid metabolism.

Question 32

What is the role of pyruvate in liver metabolism?

Answer 32

Pyruvate is used by the liver for gluconeogenesis to synthesize glucose.

Question 33

How does excess NADH affect the conversion of lactate to pyruvate?

Answer 33

High levels of NADH inhibit the conversion of lactate to pyruvate, and in some cases, the reverse reaction may occur, recycling NADH to NAD+ and causing a drop in pyruvate levels.

Question 34

How does alcohol consumption contribute to hypoglycemia?

Answer 34

Alcohol causes a low NAD+/NADH ratio, which results in the inhibition of gluconeogenesis (no production of glucose by the liver) and inhibits the conversion of lactate to pyruvate, leading to a depletion of required compounds for gluconeogenesis.

Question 35

What are the consequences of impaired gluconeogenesis caused by alcohol consumption?

Answer 35

Impaired gluconeogenesis leads to a drop in blood glucose levels, resulting in hypoglycemia.

Question 36

How is normal blood glucose maintained in the body?

Answer 36

Normal blood glucose is maintained through processes such as intestinal absorption, glycogenolysis, and gluconeogenesis.

Question 37

What is the characteristic feature of steatosis in histology?

Answer 37

Steatosis is characterized by the presence of globules of fat that distend hepatocyte cytoplasm without evidence of cell injury.

Question 38

What is the distinguishing feature of steatohepatitis in histology?

Answer 38

Steatohepatitis is characterized by the presence of steatosis (fat accumulation) along with balloon degeneration of hepatocytes, often containing Mallory-Denk bodies.

Question 39

What does the van Gieson stain show in histology?

Answer 39

The van Gieson stain highlights pericellular fibrosis (cirrhosis) in steatohepatitis, represented by red coloration around hepatocytes.

Question 40

Why do patients with alcoholic liver disease (ALD) present to the hospital?

Answer 40

Patients with ALD may present to the hospital due to alcoholic hepatitis, which is characterized by acute inflammation of the liver and jaundice. In some cases, patients with ALD may also present with decompensated cirrhosis, where the liver fails to function properly.

Question 41

How do alcohol metabolites damage the liver?

Answer 41

Alcohol metabolites, such as acetaldehyde and formic acid, can cause oxidative stress, inflammation, and injury to liver cells, leading to various forms of liver damage including steatohepatitis and cirrhosis.

Question 42

What is the underlying mechanism of fatty liver steatosis in alcohol metabolism?

Answer 42

Fatty liver steatosis in alcohol metabolism is caused by a low NAD+/NADH ratio, which leads to a shift from fatty acid catabolism to fatty acid synthesis. This results in the inhibition of β-oxidation and an increase in Acetyl CoA levels, stimulating fatty acid synthesis.

Question 43

How does ethanol contribute to the development of fatty liver?

Answer 43

Ethanol stimulates the uptake of exogenous hepatic fatty acids by upregulating hepatic fatty acid transporter proteins.

Question 44

What happens to fatty acids in the liver during steatosis?

Answer 44

Fatty acids are incorporated into triglycerides, which accumulate in the cytoplasm of hepatocytes, leading to steatosis.

Question 45

What are the key features of steatohepatitis?

Answer 45

Steatohepatitis is characterized by evidence of hepatic injury, including hepatocyte ballooning containing Mallory-Denk bodies, infiltrating immune cells, and fibrosis.

Question 46

How does alcohol induce liver inflammation in steatohepatitis?

Answer 46

Alcohol induces resident Kupffer cell macrophages to switch to a proinflammatory M1 form, releasing inducers of inflammation such as TNF. This attracts inflammatory cells from circulation, leading to liver inflammation. Kupffer cell macrophages are also a significant source of reactive oxygen species, exacerbating liver redox stress.

Question 47

What are the consequences of chronic inflammation and sustained fibrogenesis in the liver?

Answer 47

Chronic inflammation and sustained fibrogenesis lead to extensive scarring of liver tissue, which replaces liver parenchyma and severely compromises the liver’s vascular architecture.

Question 48

How does cirrhosis develop?

Answer 48

Cirrhosis development involves two phases: the compensated phase, where part of the liver remains undamaged and compensates for damaged regions, and the decompensated phase, where scar tissue fully envelopes the organ. The decompensated phase is characterized by portal hypertension and/or liver failure

Question 49

What role do hepatic stellate cells play in cirrhosis?

Answer 49

Hepatic stellate cells, which are usually quiescent lipid-storing cells, become activated following hepatic injury and become the principal source for the deposition of extracellular components that characterize fibrosis in cirrhosis.

Question 50

What is the contribution of hepatic stellate cells to inflammation in cirrhosis?

Answer 50

Hepatic stellate cells also release pro-inflammatory molecules, contributing to the inflammatory response associated with cirrhosis.

Question 51

When does alcohol withdrawal typically occur after an abrupt reduction?

Answer 51

Alcohol withdrawal can occur anywhere from 6 to 72 hours after an abrupt reduction.

Question 52

When does moderate to severe alcohol withdrawal tend to occur and what is the associated mortality rate?

Answer 52

Moderate to severe alcohol withdrawal tends to occur at 48 hours and carries a 15% mortality rate.

Question 53

What are the symptoms associated with alcohol withdrawal? (HITS)

Answer 53

The symptoms of alcohol withdrawal include Hallucinations, Insomnia and increased vital signs, Tremens delirium, and Shakes, Sweats, Seizures.

Question 54

What are the assessment tools used for alcohol withdrawal?

Answer 54

The CIWA (Clinical Institute Withdrawal Assessment) score and SADQ (Severity of Alcohol Dependence) score are commonly used assessment tools for alcohol withdrawal.

Question 55

What is Wernicke’s Encephalopathy and what can lead to its occurrence?

Answer 55

Wernicke’s Encephalopathy is caused by thiamine (Vitamin B1) depletion, often due to poor nutrition. It can also occur in conditions such as eating disorders and prolonged fasting.

Question 56

How can Wernicke’s Encephalopathy be prevented and treated?

Answer 56

Wernicke’s Encephalopathy can be prevented by administering thiamine intravenously for 48 hours, followed by oral thiamine. If left untreated, it can progress to Korsakoff’s psychosis, which causes irreversible brain damage.

Question 57

What is the role of thiamine in the body and how does alcohol interfere with its uptake?

Answer 57

Thiamine is an essential nutrient and a cofactor in carbohydrate metabolism. Alcohol interferes with the active transport system and uptake of thiamine, leading to low levels in alcoholics due to poor diet.